Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Фев. 13, 2025
Abstract
The
rapid
advancement
of
single-cell
technologies
has
created
an
urgent
need
for
effective
methods
to
integrate
and
harmonize
data.
Technical
biological
variations
across
studies
complicate
data
integration,
while
conventional
tools
often
struggle
with
reliance
on
gene
expression
distribution
assumptions
over-correction.
Here,
we
present
scCobra,
a
deep
generative
neural
network
designed
overcome
these
challenges
through
contrastive
learning
domain
adaptation.
scCobra
effectively
mitigates
batch
effects,
minimizes
over-correction,
ensures
biologically
meaningful
integration
without
assuming
specific
distributions.
It
enables
online
label
transfer
datasets
allowing
continuous
new
retraining.
Additionally,
supports
effect
simulation,
advanced
multi-omic
scalable
processing
large
datasets.
By
integrating
harmonizing
from
similar
studies,
expands
the
available
investigating
problems,
improving
cross-study
comparability,
revealing
insights
that
may
be
obscured
in
isolated
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(19)
Опубликована: Май 1, 2023
Single-cell
proteomics
has
emerged
as
a
powerful
method
to
characterize
cellular
phenotypic
heterogeneity
and
the
cell-specific
functional
networks
underlying
biological
processes.
However,
significant
challenges
remain
in
single-cell
for
analysis
of
proteoforms
arising
from
genetic
mutations,
alternative
splicing,
post-translational
modifications.
Herein,
we
have
developed
highly
sensitive
functionally
integrated
top–down
comprehensive
single
cells.
We
applied
this
muscle
fibers
(SMFs)
resolve
their
heterogeneous
proteomic
properties
at
level.
Notably,
detected
large
(>200
kDa)
SMFs.
Using
SMFs
obtained
three
distinct
muscles,
found
fiber-to-fiber
among
sarcomeric
which
can
be
related
heterogeneity.
Importantly,
multiple
isoforms
myosin
heavy
chain
(~223
kDa),
motor
protein
that
drives
contraction,
with
high
reproducibility
enable
classification
individual
fiber
types.
This
study
reveals
cell
establishes
direct
relationship
between
types,
highlighting
potential
uncovering
molecular
underpinnings
cell-to-cell
variation
complex
systems.
Nature Methods,
Год журнала:
2023,
Номер
20(7), С. 1058 - 1069
Опубликована: Май 29, 2023
Abstract
Highly
multiplexed
imaging
holds
enormous
promise
for
understanding
how
spatial
context
shapes
the
activity
of
genome
and
its
products
at
multiple
length
scales.
Here,
we
introduce
a
deep
learning
framework
called
CAMPA
(Conditional
Autoencoder
Multiplexed
Pixel
Analysis),
which
uses
conditional
variational
autoencoder
to
learn
representations
molecular
pixel
profiles
that
are
consistent
across
heterogeneous
cell
populations
experimental
perturbations.
Clustering
these
pixel-level
identifies
subcellular
landmarks,
can
be
quantitatively
compared
in
terms
their
size,
shape,
composition
relative
organization.
Using
high-resolution
immunofluorescence,
this
reveals
organization
changes
upon
perturbation
RNA
synthesis,
processing
or
uncovers
links
between
membraneless
organelles
cell-to-cell
variability
bulk
synthesis
rates.
By
capturing
interpretable
cellular
phenotypes,
anticipate
will
greatly
accelerate
systematic
mapping
multiscale
atlases
biological
identify
rules
by
physiology
disease.
Nature Aging,
Год журнала:
2024,
Номер
4(7), С. 998 - 1013
Опубликована: Май 30, 2024
Abstract
Organismal
aging
involves
functional
declines
in
both
somatic
and
reproductive
tissues.
Multiple
strategies
have
been
discovered
to
extend
lifespan
across
species.
However,
how
age-related
molecular
changes
differ
among
various
tissues
those
lifespan-extending
slow
tissue
distinct
manners
remain
unclear.
Here
we
generated
the
transcriptomic
Cell
Atlas
of
Worm
Aging
(CAWA,
http://mengwanglab.org/atlas
)
wild-type
long-lived
strains.
We
cell-specific,
signatures
all
germ
cell
types.
developed
clocks
for
different
quantitatively
determined
three
pro-longevity
distinctively.
Furthermore,
through
genome-wide
profiling
alternative
polyadenylation
(APA)
events
tissues,
cell-type-specific
APA
during
revealed
these
are
differentially
affected
by
strategies.
Together,
this
study
offers
fundamental
insights
into
provides
a
valuable
resource
in-depth
understanding
diversity
mechanisms.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 6, 2024
Abstract
Recent
advancements
for
simultaneously
profiling
multi-omics
modalities
within
individual
cells
have
enabled
the
interrogation
of
cellular
heterogeneity
and
molecular
hierarchy.
However,
technical
limitations
lead
to
highly
noisy
multi-modal
data
substantial
costs.
Although
computational
methods
been
proposed
translate
single-cell
across
modalities,
broad
applications
still
remain
impeded
by
formidable
challenges.
Here,
we
propose
scButterfly,
a
versatile
cross-modality
translation
method
based
on
dual-aligned
variational
autoencoders
augmentation
schemes.
With
comprehensive
experiments
multiple
datasets,
provide
compelling
evidence
scButterfly’s
superiority
over
baseline
in
preserving
while
translating
datasets
various
contexts
revealing
cell
type-specific
biological
insights.
Besides,
demonstrate
extensive
scButterfly
integrative
analysis
single-modality
data,
enhancement
poor-quality
multi-omics,
automatic
type
annotation
scATAC-seq
data.
Moreover,
can
be
generalized
unpaired
training,
perturbation-response
analysis,
consecutive
translation.
Abstract
Single-cell
sequencing
datasets
are
key
in
biology
and
medicine
for
unraveling
insights
into
heterogeneous
cell
populations
with
unprecedented
resolution.
Here,
we
construct
a
single-cell
multi-omics
map
of
human
tissues
through
in-depth
characterizations
from
five
omics,
spatial
transcriptomics,
two
bulk
omics
across
125
healthy
adult
fetal
tissues.
We
its
complement
web-based
platform,
the
Single
Cell
Atlas
(SCA,
www.singlecellatlas.org
),
to
enable
vast
interactive
data
exploration
deep
signatures
The
atlas
resources
database
queries
aspire
serve
as
one-stop,
comprehensive,
time-effective
resource
various
studies.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 7, 2024
Abstract
Characterizing
the
transcriptional
and
translational
gene
expression
patterns
at
single-cell
level
within
their
three-dimensional
(3D)
tissue
context
is
essential
for
revealing
how
genes
shape
structure
function
in
health
disease.
However,
most
existing
spatial
profiling
techniques
are
limited
to
5-20
µm
thin
sections.
Here,
we
developed
Deep-STARmap
Deep-RIBOmap,
which
enable
3D
situ
quantification
of
thousands
transcripts
corresponding
translation
activities,
respectively,
200-µm
thick
blocks.
This
achieved
through
scalable
probe
synthesis,
hydrogel
embedding
with
efficient
anchoring,
robust
cDNA
crosslinking.
We
first
utilized
combination
multicolor
fluorescent
protein
imaging
simultaneous
molecular
cell
typing
neuron
morphology
tracing
mouse
brain.
also
demonstrate
that
facilitates
comprehensive
quantitative
analysis
tumor-immune
interactions
human
skin
cancer.